Accurate detection of de novo and transmitted indels within exome-capture data using micro-assembly

We present an open-source algorithm, Scalpel, which combines mapping and assembly for sensitive and specific discovery of indels in exome-capture data. A detailed repeat analysis coupled with a self-tuning k-mer strategy allows Scalpel to outperform other state-of-the-art approaches for indel discovery, particularly in regions containing near-perfect repeats. We analyze 593 families from the Simons Simplex Collection and demonstrate Scalpel's power to detect long (≥20bp) transmitted events, and enrichment for de novo likely gene-disrupting indels in autistic children.